Side Effects of Propecia (finasteride)

Propecia (finasteride) is used to treat male pattern baldness or androgenetic alopecia in males only. Propecia works by lowering levels of a hormone that shrinks hair follicles, called dihydrotestosterone (DHT).

It slows hair loss in about 88% of men and helps hair regrow in about 66%. Another finasteride oral dosage form, Proscar or 5 mg finasteride tablets are FDA approved only for the treatment of benign prostatic hyperplasia (BPH) and should not be used for androgenetic alopecia. Do not confuse these finasteride tablets.

Common side effects of Propecia include

• breast enlargement,
• decreased sex drive,
• erectile dysfunction, and
• ejaculation disorders.

Serious side effects of Propecia include

• increased risk of high-grade prostate cancer, and
• increased risk for male breast cancer.

Drug interactions of Propecia include carbamazepine, rifampin, and St. John's wort, which may reduce blood levels of Propecia by increasing its breakdown in the liver. Itraconazole, erythromycin and similar drugs increase blood levels of Propecia.

Propecia should not be used or handled by pregnant mothers due to the potential hazard to the male fetus. Propecia prevents the conversion of testosterone to DHT, a hormone which is necessary for the development of male genitalia.

It is not known if Propecia is excreted in breast milk. Propecia is not indicated for use by women and should not be used while breastfeeding.

The most common side effects associated with finasteride are:

• breast enlargement,
• decreased libido,
• erectile dysfunction, and
• ejaculation disorders.

Serious side effects include increased risk of high-grade prostate cancer, and increased risk for male breast cancer.

Propecia (1 mg finasteride) was approved by the FDA for the treatment of male pattern baldness in December 1997. Another finasteride oral dosage form, Proscar or 5 mg finasteride tablets are FDA approved only for the treatment of benign prostatic hyperplasia (BPH) and should not be used for androgenetic alopecia. Do not confuse these finasteride tablets.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Clinical Studies For Propecia (Finasteride 1 mg) In The Treatment Of Male Pattern Hair Loss

In three controlled clinical trials for Propecia of 12-month duration, 1.4% of patients taking Propecia (n=945) were discontinued due to adverse experiences that were considered to be possibly, probably or definitely drug-related (1.6% for placebo; n=934).

Clinical adverse experiences that were reported as possibly, probably or definitely drug-related in ≥1% of patients treated with Propecia or placebo are presented in Table 1.

TABLE 1: Drug-Related Adverse Experiences for Propecia (finasteride 1 mg) in Year 1 (%)
MALE PATTERN HAIR LOSS

• Integrated analysis of clinical adverse experiences showed that during treatment with Propecia, 36 (3.8%) of 945 men had reported one or more of these adverse experiences as compared to 20 (2.1%) of 934 men treated with placebo (p=0.04).
•  Resolution occurred in men who discontinued therapy with Propecia due to these side effects and in most of those who continued therapy.
• The incidence of each of the above adverse experiences decreased to ≤0.3% by the fifth year of treatment with Propecia.
• In a study of finasteride 1 mg daily in healthy men, a median decrease in ejaculate volume of 0.3 mL (- 11%) compared with 0.2 mL (-8%) for placebo was observed after 48 weeks of treatment.
• Two other studies showed that finasteride at 5 times the dosage of Propecia (5 mg daily) produced significant median decreases of approximately 0.5 mL (-25%) compared to placebo in ejaculate volume, but this was reversible after discontinuation of treatment.
• In the clinical studies with Propecia, the incidences for breast tenderness and enlargement, hypersensitivity reactions, and testicular pain in finasteride-treated patients were not different from those in patients treated with placebo.

Controlled Clinical Trials And Long-Term Open Extension Studies For Proscar® (Finasteride 5 mg) And AVODART (Dutasteride) In The Treatment Of Benign Prostatic Hyperplasia

In the Proscar Long-Term Efficacy and Safety Study (PLESS), a 4-year controlled clinical study, 3040 patients between the ages of 45 and 78 with symptomatic BPH and an enlarged prostate were evaluated for safety over a period of 4 years (1524 on Proscar 5 mg/day and 1516 on placebo). 3.7% (57 patients) treated with Proscar 5 mg and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions.

Table 2 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on Proscar was ≥1% and greater than placebo over the 4 years of the study. In years 2-4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder.

TABLE 2: Drug-Related Adverse Experiences for Proscar (finasteride 5 mg)
BENIGN PROSTATIC HYPERPLASIA

• The adverse experience profiles in the 1-year, placebo-controlled, Phase III BPH studies and the 5-year open extensions with Proscar 5 mg and PLESS were similar.
• There is no evidence of increased sexual adverse experiences with increased duration of treatment with Proscar 5 mg. New reports of drug-related sexual adverse experiences decreased with duration of therapy.
• During the 4- to 6-year placebo- and comparator-controlled Medical Therapy of Prostatic Symptoms (MTOPS) study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with Proscar but no cases in men not treated with Proscar. During the 4-year placebo-controlled PLESS study that enrolled 3040 men, there were 2 cases of breast cancer in placebo-treated men, but no cases were reported in men treated with Proscar.
• During the 7-year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with Proscar, and 1 case of breast cancer in men treated with placebo. The relationship between long-term use of finasteride and male breast neoplasia is currently unknown.
• The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 healthy men ≥55 years of age with a normal digital rectal examination and a PSA ≤3.0 ng/mL.
• Men received either Proscar (finasteride 5 mg) or placebo daily.
• Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study.
• The incidence of Gleason score 8-10 prostate cancer was higher in men treated with finasteride (1.8%) than in those treated with placebo (1.1%).
• In a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor [AVODART (dutasteride)], similar results for Gleason score 8-10 prostate cancer were observed (1% dutasteride vs 0.5% placebo). The clinical significance of these findings with respect to use of Propecia by men is unknown.
• No clinical benefit has been demonstrated in patients with prostate cancer treated with Proscar. Proscar is not approved to reduce the risk of developing prostate cancer.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Propecia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Hypersensitivity Reaction

hypersensitivity reactions such as rash, pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face);

Reproductive System

sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders; male infertility and/or poor seminal quality (normalization or improvement of seminal quality has been reported after discontinuation of finasteride); testicular pain.

Neoplasms

male breast cancer;

Breast Disorders

breast tenderness and enlargement;

Nervous System/Psychiatric

depression

Cytochrome P450-Linked Drug Metabolizing Enzyme System

• No drug interactions of clinical importance have been identified.
• Finasteride does not appear to affect the cytochrome P450-linked drug-metabolizing enzyme system.
• Compounds that have been tested in man include
  • antipyrine,
  • digoxin,
  • propranolol,
  • theophylline, and warfarin and no clinically meaningful interactions were found.

Other Concomitant Therapy

Although specific interaction studies were not performed, finasteride doses of 1 mg or more were concomitantly used in clinical studies with

• acetaminophen,
• acetylsalicylic acid,
• α-blockers,
• analgesics,
• angiotensin-converting enzyme (ACE) inhibitors,
• anticonvulsants,
• benzodiazepines,
• beta blockers,
• calcium-channel blockers,
•  cardiac nitrates,
• diuretics,
• H₂ antagonists,
• HMG-CoA reductase inhibitors,
• prostaglandin synthetase inhibitors (also referred to as NSAIDs), and
• quinolone anti-infectives without evidence of clinically significant adverse interactions.